Molecular Pathways
The machinery of aging.
The mechanistic layer between what you take and what ages — the pathways compounds act through, each linked to the hallmarks it moves and the compounds that engage it.
Mechanistic families
19pathways
- NAD⁺ & Sirtuins632%
- Nutrient Sensing316%
- Mitochondrial Quality421%
- Cellular Defense421%
- Signaling & Repair211%
Pathway families · derived from the pathway registry
How compounds actually move a hallmark.
The mechanistic layer between what you take and what ages — the pathways (PINK1/Parkin, SIRT3, NRF2, AMPK, mTOR, NAD⁺ …) that compounds engage. Each pathway links to the hallmarks it acts on and every compound that targets it.
Mechanism families
19 pathways across 5 families
The verbs behind the network below
- Sirtuin axis6
- Nutrient sensing3
- Mitophagy & mitochondria4
- Cellular defense4
- Intercellular signaling2
NAD⁺ & Sirtuins
The NAD⁺-dependent deacetylases and repair enzymes that translate energy status into DNA repair, mitophagy, and epigenetic maintenance.
The central redox and signaling coenzyme every sirtuin and PARP depends on — and it falls ~50% between ages 40 and 60.
The NAD⁺-dependent deacetylase that couples energy status to epigenetic maintenance, autophagy, and inflammatory restraint.
The mitochondrial sirtuin that deacetylates metabolic enzymes and enables mitochondrial quality control.
The chromatin sirtuin governing DNA double-strand-break repair, telomere maintenance, and genome stability.
DNA-damage sensors that repair strand breaks by consuming large amounts of NAD⁺.
An NAD⁺-degrading ectoenzyme that rises with age and inflammation, draining the NAD⁺ pool.
Nutrient Sensing
The growth-vs-repair switches — mTOR, AMPK, FOXO — that decide whether a cell builds or maintains.
The master growth kinase — when active it builds; when inhibited, cells shift to repair and autophagy.
The cellular low-energy sensor that switches on fat burning, mitochondrial biogenesis, and autophagy.
A longevity-associated transcription factor that turns on stress-resistance, antioxidant, and repair genes.
Mitochondrial Quality
Mitophagy and biogenesis pathways that clear damaged mitochondria and build new ones.
The sensor–tag pair that marks damaged mitochondria for selective recycling (mitophagy).
The master regulator of mitochondrial biogenesis — the making of new mitochondria.
The transcription factor that switches on the autophagy–lysosome clearance program.
The kinase that initiates autophagosome formation — the first committed step of autophagy.
Cellular Defense
The antioxidant and inflammatory master switches — NRF2, NF-κB, the inflammasome — that set redox and inflammatory tone.
The master antioxidant switch that turns on 200+ cytoprotective and detoxification genes.
The central pro-inflammatory transcription factor whose chronic activation drives inflammaging.
The innate-immune sensor complex that releases IL-1β and IL-18 — a key inflammaging amplifier.
The body's most abundant endogenous antioxidant — depleted ~10–15% per decade after age 20.
Signaling & Repair
Vascular, neuronal, and proteostasis signaling nodes that compounds act through.
The endothelial enzyme that makes nitric oxide — the signal that relaxes blood vessels.
A multifunction kinase whose inhibition promotes autophagy and reduces tau phosphorylation.
How it connects
One compound, many pathways.
The same molecule often engages several pathways at once — which is why a small, well-chosen stack can cover many hallmarks. Explore the synergy map: hover a node to trace the pathways it touches.
Hover any compound to see its synergy connections · Click to open library deep-dive
| Compound A | Compound B | Strength | Mechanism |
|---|---|---|---|
| NMN | Resveratrol | strong | NMN restores NAD+ substrate for SIRT1/3. Ca-AKG supplies α-KG for TET demethylation. Together they create a positive feedback loop: restored mitochondrial function increases NAD+ production, which further amplifies sirtuin activity. |
| NMN | Ca-AKG | strong | NMN restores NAD+ substrate for SIRT1/3. Ca-AKG supplies α-KG for TET demethylation. Together they create a positive feedback loop: restored mitochondrial function increases NAD+ production, which further amplifies sirtuin activity. |
| NMN | R-ALA | strong | NMN restores NAD+ for sirtuin/mitochondrial function; R-ALA supports pyruvate dehydrogenase complex. |
| NMN | CoQ10 | strong | NMN restores the NAD+ that donates electrons at Complex I; CoQ10 shuttles those electrons onward to Complex III. They support the same oxidative-phosphorylation chain at complementary steps. |
| NMN | Urolithin A | strong | Urolithin A triggers mitophagy to clear damaged mitochondria while NMN restores the NAD+ that powers their replacement and function — the recycle-and-refuel halves of mitochondrial quality control. |
| NMN | GlyNAC | moderate | Resveratrol activates AMPK and SIRT1, inducing autophagy. GlyNAC provides glutathione to manage the increased oxidative load from lysosomal activity during bulk autophagy. NMN ensures the NAD+ substrate pool is not depleted by increased PARP/SIRT demand. |
| NMN | Taurine | moderate | Taurine supports mitochondrial osmotic and antioxidant balance while NMN replenishes NAD+ for sirtuin-driven DNA repair — two currencies that both fall with age, topped up together. |
| NMN | Spermidine | moderate | Spermidine EP300 inhibition activates autophagy gene programs; NMN fuels sirtuin-driven mitophagy — dual-pathway organelle recycling. |
| NMN | Fisetin | moderate | Senescent cells are major NAD+ consumers via CD38; fisetin clears them, so NMN then replenishes NAD+ into a lower-demand system — senolysis and NAD+ repletion reinforce each other. |
| NMN | Berberine | moderate | Berberine activates AMPK while NMN restores NAD+/SIRT1 — a reciprocally reinforcing energy-sensing loop (AMPK raises NAD+; SIRT1 sustains AMPK) that drives mitochondrial biogenesis and mitophagy. |
| NMN | Pterostilbene | moderate | Pterostilbene — a more bioavailable resveratrol analog — activates SIRT1, which can only work with the NAD+ that NMN restores; the pair supplies activator and cofactor for the same sirtuin axis. |
| Resveratrol | Ca-AKG | strong | NMN restores NAD+ substrate for SIRT1/3. Ca-AKG supplies α-KG for TET demethylation. Together they create a positive feedback loop: restored mitochondrial function increases NAD+ production, which further amplifies sirtuin activity. |
| Resveratrol | Pterostilbene | strong | Both are stilbene SIRT1 activators; pterostilbene's methylation gives it a longer half-life and higher bioavailability, complementing resveratrol's broader polyphenol activity on the shared sirtuin axis. |
| Resveratrol | Spermidine | moderate | Spermidine induces autophagy through eIF5A/TFEB signalling independently of the sirtuins, while resveratrol induces it via SIRT1/AMPK — two mechanistically distinct autophagy inducers converging on the same clean-up program. |
| Resveratrol | Fisetin | moderate | Fisetin clears senescent cells and, like resveratrol, is a polyphenol antioxidant; resveratrol adds SIRT1 activation — senolytic clearance alongside sirtuin-mediated stress resistance. |
| Resveratrol | Berberine | moderate | Both push AMPK — berberine directly and resveratrol via SIRT1 — reinforcing the caloric-restriction-mimetic signal that shifts metabolism toward oxidation and autophagy. |
| Resveratrol | Omega-3 | moderate | Omega-3 supplies the EPA/DHA substrate for pro-resolving mediators (resolvins) while resveratrol suppresses NF-κB via SIRT1 — inflammation is resolved and dampened from two directions. |
| GlyNAC | Sulforaphane | strong | Sulforaphane activates NRF2 transcription of defense genes; GlyNAC replenishes the glutathione pool those genes require; R-ALA regenerates oxidized glutathione and vitamin C/E. The three compounds address upstream activation, substrate availability, and recycling simultaneously. |
| GlyNAC | R-ALA | strong | Sulforaphane activates NRF2 transcription of defense genes; GlyNAC replenishes the glutathione pool those genes require; R-ALA regenerates oxidized glutathione and vitamin C/E. The three compounds address upstream activation, substrate availability, and recycling simultaneously. |
| Sulforaphane | R-ALA | moderate | Sulforaphane activates NRF2 transcription of defense genes; GlyNAC replenishes the glutathione pool those genes require; R-ALA regenerates oxidized glutathione and vitamin C/E. The three compounds address upstream activation, substrate availability, and recycling simultaneously. |
| Sulforaphane | Omega-3 | moderate | Sulforaphane activates NRF2 to induce endogenous antioxidant and phase-II defences, while omega-3 EPA/DHA resolve inflammation — antioxidant defence paired with inflammation resolution. |
| CoQ10 | R-ALA | strong | R-alpha-lipoic acid is a redox cofactor that helps regenerate oxidized ubiquinone back to active ubiquinol, extending CoQ10's antioxidant and electron-carrying capacity in the mitochondrion. |
| Spermidine | Urolithin A | moderate | Spermidine induces general autophagy via EP300; urolithin A specifically triggers mitophagy via PINK1/Parkin. Complementary routes to organelle quality control. |